A prognostic molecule found in tumor cells from breast cancer patients was identified as fatty acid synthase (FAS). See Kuhajda et al. (1994) “Fatty acid synthesis: a potential selective target for antineoplastic therapy.” Proc Natl Acad Sci USA., 91(14):6379-83. FAS is an approximately 270-kDa polypeptide, and tumor fatty acid synthase oxidizes NADPH in a malonyl-CoA-dependent fashion and synthesized fatty acids composed of 80% palmitate, 10% myristate, and 10% stearate from acetyl-CoA, malonyl-CoA, and NADPH with a specific activity of 624 nmol of NADPH oxidized per min per mg. Studies with tumor cell lines with elevated fatty acid synthase expression demonstrated that fatty acid synthase increases occur in the context of overall cellular increases in endogenous fatty acid synthesis. FAS was also identified as the target for inhibition by cerulenin-mediated inhibition of acylglycerol synthesis in cells.
Subsequently, FAS was recognized as playing the key role in enzyme mediated, de novo fatty acid synthesis. FAS expression has been shown to be involved in carcinogenesis of human malignancies beyond breast to include colorectal and prostate carcinomas. See for example, Shurbaji et al. (1996) “Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer.” Hum Pathol. 27(9):917-21, where an affinity purified FAS antibody was used to examine primary prostate cancers by immunohistochemistry.
Two archetypal monoclonal antibodies (MAbs) which bind FAS have been identified and used in an enzyme linked immunosorbent assay (ELISA) to quantify FAS. See Wang et al., “A new model ELISA, based on two monoclonal antibodies, for quantification of fatty acid synthase.” (2002) J Immunoassay Immunochem. 23(3):279-92. A MAb identified as M6 was used as the capture antibody in the ELISA while a MAb identified as M3 was labeled and used as a detector antibody. The ELISA based on this two MAb combination was recognized as an improvement over previous assays based on an earlier polyclonal-monoclonal combination ELISA described by Wang et al. (“Two-site ELISA for the quantitative determination of fatty acid synthase.” Clin Chim Acta. 304(1-2):107-15, (2002)).
Innocenzi et al. (“Fatty acid synthase expression in melanoma.” J Cutan Pathol. 30(1):23-8, (2003)) also describe experiments with use of the M6 antibody. Krontiras et al. (“Fatty acid synthase expression is increased in neoplastic lesions of the oral tongue.” Head Neck 21(4):325-9, (1999)) describe the use of antibodies from ChekTec of Baltimore, Md., which offered M3 and M6 as anti-OA-519 antibodies. Pizer et al. (“Increased fatty acid synthase as a therapeutic target in androgen-independent prostate cancer progression.” Prostate 47(2):102-10 (2001)) used antibodies as described in U.S. Pat. No. 5,864,011, which is related to U.S. Pat. No. 5,759,791, as discussed below.
The above discussion and citation of documents herein is not intended as an admission that any is pertinent prior art. All statements as to the date or representation as to the contents of documents is based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of the documents.